It has recently been suggested that advanced glycosylation end-products (AGEs) are formed in the peritoneum in patients on CAPD. However, the exact location of AGE accumulation, the relation with the duration of CAPD and its pathophysiological role in CAPD remain unclear. If the peritoneum is glycosylated, it could bring about altered peritoneal function. Therefore, the aim of this study is to clarify the localization of AGEs in the peritoneum in accordance with the duration of CAPD and to examine its relation to the peritoneal permeability. Fifteen non-diabetic patients were divided into three groups (each 5 patients) on the basis of the mean duration (D) of CAPD (Group 1, D = 0 month; Group II, D = 34 months; Group III, D = 84 months). The AGE staining by monoclonal anti-AGE antibody in the peritoneum and the four-hour peritoneal equilibration test (PET) were compared among these groups. AGE was absent or found only weakly in Group I. However, in groups II and III, AGE was moderately or strongly positive especially in the vascular walls and it was dominant in group III. PET revealed that peritoneal permeability for glucose, creatinine, beta2-microglobulin and albumin was increased in Group II as compared to Group I, and it was further increased in Group III. The results of this study indicate that AGEs become dominantly accumulated in the vascular wall in accordance with the prolongation of CAPD treatment, and this might play some roles for the increased permeability of the peritoneal membrane in CAPD.

Background-Remnant lipoproteins are atherogenic, but assays of remnants have not been available in routine clinical laboratories because of the lack of practical and validated methods. A simple and reliable method for such an assay, using an immunochemical approach, has recently been developed. This study prospectively examined whether remnant lipoprotein levels in fasting serum, measured by our method, may have prognostic value in patients with coronary artery disease (CAD). Methods and Results-Remnant lipoprotein levels in fasting serum were measured in 135 patients with CAD by an immunoaffinity mixed gel containing anti-apolipoprotein (apo) A-1 and anti-apoB-100 monoclonal antibodies. Patients were followed up for Յ36 months until occurrence of 1 of the following clinical coronary events: recurrent or refractory angina pectoris requiring coronary revascularization, nonfatal myocardial infarction, or cardiac death. Kaplan-Meier analysis demonstrated a significantly higher probability of developing coronary events in patients with the highest tertile of remnant levels (Ͼ5.1 mg cholesterol/dL; 75th percentile of distribution of remnant levels) than in those with the lowest tertile of remnant levels (Յ3.3 mg cholesterol/dL; 50th percentile of the distribution). Higher levels of remnants were a significant and independent predictor of developing coronary events in multivariate Cox hazard analysis including the following covariates: extent of coronary artery stenosis, age, sex, smoking, hypertension, diabetes mellitus, hypercholesterolemia, low HDL cholesterol, and hypertriglyceridemia. Conclusions-Higher levels of remnant lipoproteins in fasting serum predict future coronary events in patients with CAD independently of other risk factors. Thus, measurement of fasting remnant levels, assessed by the current immunoseparation method, may be helpful in assessment of CAD risk. (Circulation. 1999;99:2858-2860.)

Background-The circulating levels of secretory nonpancreatic type II phospholipase A 2 (sPLA 2 ) are increased in various chronic inflammatory diseases and the increase in the levels correlates with the disease severity. sPLA 2 may possibly play a role in atherogenesis and is highly expressed in atherosclerotic arterial walls that are known to have inflammatory features. Thus, this study prospectively examined whether circulating levels of sPLA 2 may have a significant risk and prognostic values in patients with coronary artery disease (CAD). Methods and Results-Plasma levels of sPLA 2 were measured in 142 patients with CAD and in 93 control subjects by a radioimmunoassay. The sPLA 2 levels had a significant and positive relations with serum levels of C-reactive protein, a marker of systemic inflammation, and with the number of the traditional coronary risk factors associated with individuals. Multivariate logistic regression analysis showed that higher levels of sPLA 2 (Ͼ246 ng/dL; 75th percentile of sPLA 2 distribution in controls) were a significant and independent risk factor for the presence of CAD. In multivariate Cox hazard analysis, the higher levels of sPLA 2 were a significant predictor of developing coronary events (ie, coronary revascularization, myocardial infarction, coronary death) during a 2-year follow-up period in patients with CAD independent of other risk factors, including CRP levels, an established inflammatory predictor. Conclusions-The increase in circulating levels of sPLA 2 is a significant risk factor for the presence of CAD and predicts clinical coronary events independent of other risk factors in patients with CAD; these results may reflect possible relation of sPLA 2 levels with inflammatory activity in atherosclerotic arteries. (Circulation. 1999;100:1280-1284.)

Background-This study was designed to evaluate the plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with unstable angina and investigate whether there is a relationship between these levels and unfavorable outcome. Methods and Results-The plasma TF and free TFPI antigen levels were determined in plasma samples taken from 51 patients with unstable angina, 56 with stable exertional angina, and 55 with chest pain syndrome. The plasma TF and free TFPI antigen levels were higher in the unstable angina group than in the stable exertional angina and chest pain syndrome group. There was a good correlation between TF and TFPI. We established borderline as maximum level in the patients with chest pain syndrome. Seven patients (of the 22 in the high TF group) required revascularization to control their unstable angina during in-hospital stay. On the other hand, only 1 of the 29 patients in the low TF group required myocardial revascularization. Four patients of the 14 patients in the high free TFPI group required myocardial revascularization during in-hospital stay, and 4 of the 37 patients in the low free TFPI group required myocardial revascularization. We compared the TF and free TFPI levels between the cardiac event (ϩ) group and cardiac event (Ϫ) group. TF levels were significantly higher in the cardiac event (ϩ) group than in the cardiac event (Ϫ) group. Conclusions-We have demonstrated that not only the plasma TF levels but also the plasma-free TFPI levels are elevated in patients with unstable angina. Patients with unstable angina and heightened TF and free TFPI are at increased risk for unfavorable outcomes. The heightened TF level was a more important predictor in patients with unstable angina.